Struma Ovarii (SO) is the most frequent monodermal ovarian teratoma and is defined as a teratoma composed primarily or exclusively of thyroid tissue. Malignant SO is extremely rare and seen in about 5% of cases (19 cases reported from 1990-2008). [1, 2] In addition, these malignant SO only account for 0.1-0.5% of all ovarian tumors. Malignant SO tends only to involve one ovary and on gross examination has the similar red brown appearing tissue as in the thyroid. [2] Classifying SO as malignant has been a controversial topic as earlier studies used metastasis and invasion as the only diagnostic criteria but more recent studies have suggested that the criteria for malignancy should be the same as that in the thyroid gland. Metastatic disease can be seen most often in the peritoneum but have also been reported in the liver, bone, lung, and brain. Our case was very interesting, as the incidence of metastasis from SO to soft tissue is extremely rare and has only been described in a couple of case reports (5 cases reported in an article in 1989). [5] When working up a case of malignant SO, it is necessary to rule out a metastatic primary thyroid cancer to the ovary, although it is quite rare. [1]

CLINICAL PRESENTATION

The median age for women who have this disease entity to present is 41 years. [2] They typically do not present with any clinical or physical signs of disease, however, some do have signs/symptoms of hyperthyroidism. Physical examination findings are nonspecific and can include a palpable mass, swelling, pain or sensation of a mass, hydrothorax (Meig's Syndrome) and ascites. [1, 5]

HISTOLOGY

Diagnosing SO is often simple as the presence of thyroid follicles with colloid resembling that seen in the eutopic thyroid gland is quite diagnostic. Ancillary studies such as positive staining for thyroglobulin and TTF-1 and finding polarizable calcium oxalate crystals can be performed as confirmatory tests. Labeling SO as malignant, however, is quite challenging as there is uncertainty to what criteria should be used. [2]

Papillary thyroid cancer (PTC) and follicular carcinoma can both arise in SO, with PTC being the most common. The proposed histologic features to classify SO as malignant include chromatin clearing, nuclear grooves, overlapping nuclei, and pseudoinclusions for PTC and capsular/vascular invasion for follicular. [1]

Despite the controversy on how to histologically classify these tumors as malignant, the key issue is distinguishing whether these histologically malignant tumors are prone to spread beyond the ovary (biologically malignant). S.J. Robboy et al performed a study to identify clinical and/or histologic features that correlated with present or future extraovarian spread. They found that biologically malignant SO occurred in tumors that histologically had features of malignancy, that histologically were adenomas, and even those that histologically were benign thyroid tissue. However, the presence of dense fibrous adhesions, ascites, and a large tumor size (>12 cm) were findings suggestive that the patient's tumors will recur or spread at the time of surgery. [2]

The finding of peritoneal implants consisting of benign thyroid tissue, coined "benign strumatosis", is also debatable. According to WHO, this does not change the prognosis and should not be considered a sign of malignancy. Robboy, however, argues against calling this benign as a patient in their study diagnosed with this entity had many recurrences and ultimately died having widespread disease. [2]

MOLECULAR STUDIES

RET/PTC rerrangements is described as one of the initial steps in tumor pathogenesis particulary of papillary thyroid cancer. The incidence of this mutation in PTC ranges from 3%- 85% with a higher incidence in radiation induced cancers and in children. It has been suggested that this rearrangement is the cause of the nuclear and structural changes seen in classic PTC. [3] Different mutations, including RET, have been identified for thyroid cancers that have prognostic implications. Larger studies are needed in cases of malignant SO to assess whether these molecular abnormalities also have the same implications as they do in thyroid cancer. [1]

DIFFERENTIAL DIAGNOSIS

Malignant SO can sometimes be confused with sex cord-stromal tumors, in particularly the granulosa cell tumor. This most often happens when there is a more solid adenoma or when the papillary pattern of the SO resembles the moiré silk pattern of the granulosa cell tumor. Immunohistochemicals can help distinguish the two as the granulosa cell tumors are usually positive for inhibin and calretinin. [2]

TREATMENT AND PROGNOSIS

Treatment for malignant SO can range from a simple cystectomy to a hysterectomy with bilateral salpingo-oophorectomy. An initial staging work up includes an ultrasound of the thyroid, to rule out thyroid as the primary site, and serum thyroglobulin levels, marker of metastatic disease. If both are normal the patient is followed up with repeat serum thyroglobulin (every 6-12 months), neck US (every few years), and abdominal imaging (every year). If the thyroglobulin is elevated or there is evidence of metastatic disease, individuals are treated with radioactive iodine after a total thyroidectomy. The thyroid must be removed prior to starting treatment as it concentrates the radioactive iodine. [1] These patients are followed for a long time (at least one decade) as cases of recurrence 20-40 years later have been described. [1, 2] Despite the fact that these tumors are clinically malignant, the long term survival for these women is 84% at 25 years. [2]